We propose the acquisition of a 600 Mhz NMR spectrometer. The research proposed for the new instrument will improve our capability for determining high-resolution protein and nucleic acid structures in solution from two- dimensional NMR experiments. The most effective means of deriving nucleic acid and protein solution structure by using the complete relaxation matrix analysis of 2D NOE spectra to obtain numerous internuclear distances and scalar-coupling-based 2D NMR experiments to yield torsion angle constraints, in conjunction with the computational techniques of distance geometry, molecular mechanics and restrained molecular dynamics will be utilized. Reverse-detection heteronuclear 2D NMR experiments will enable resonance assignments and structural insights. Some studies necessitate the use of H2O solutions, thus requiring efforts to overcome the dynamic range problem due to water protons. The improved capabilities should also aid in our studies of ligand binding to biopolymers, thus leading to greater mechanistic insights. The major user group (with NIH support) is composed of Vladimir J. Basus (RR01695), Thomas L. James (GM39247, GM41639), George L. Kenyon (GM39552, AR17323, GM45070), Irwin D. Kuntz (RR01695, GM19267), Norman J. Oppenheimer (GM22982, CA47764), and Richard H.Shafer (CA27343).